Method of preparing choline salt of theophylline



UNITED STATES ATENT OFFICE METHOD OF PREPARING CHOLINE SALT OF THEOPHYLLINE Peter Claude Herold, East Meadow, N. 35., as-

signor, by mesne assignments, to Nepera Chemical 00., Inc., Yonkers, N. Y., a corporation of New York No Drawing. Application August 8, 1952, Serial No. 303,419

2 Claims. (Cl. 260-256) This invention relates to a choline salt of a choline chloride and potassium theophyllinate, xanthine as a new chemical compound useful each in methanol, are reacted to produce theoin medicine and more especially to the compound phyllin cholinate and potassium chloride. The

choline salt of the Xanthine theophylline which and being very soluble in water and ethanol. has good stability in air and which can thus be The compound has a molecular weight of 283 administered in liquid form. and a melting point of 176-l78 C. and responds It is a further object of the invention to proto the formula C7H'IO2N4ICsI-I14ON. Its compoduce theophyllin cholinate, which is a new chemsition is equivalent to 60% anhydrous theophylical compound useful in medicine and which has line and 40% choline base. One molecule of properties giving it advantages not shared by the new compound in 825 cc. H2O will absorb un hol nat th ophylline or other theophyllin 0.18 mols of 002 before theophylline will precipcompounds. itate.

More specifically, it is an object of the in- The new compound theophyllin cholinate can vention to produce the choline salt of theophylbe processed to pharmaceutical specialties in a line to form a medicinally valuable compound manner similar to that of theophylline ethyl- Which is vastly superior to theophylline ethyl- 2o enediamine (Aminophyllin). The dosage of enediamine and theophylline sodium glycinate. theophyllin cholinate is 33% greater than theo- A still further object of the invention resides phylline ethylenediamine and less than in procedure by means of which the new comtheophylline sodium glyoinate due to the prespound can be prepared. ence of the cholinate in the molecule which has The xanthine theophylline is used in medicine 25 good lipotropic properties, thus making the comalt ough its therapeutic value is accompanied pound particularly valuable for the treatment by certain adverse side effects. For example, of atherosclerosis, arterioschlerosis and cardiotheophylline and its previously known derivavascular diseases tives are insoluble or only slightly soluble in I claim: water and they are incompatible with digestive 1. The method of preparing theophyllin cholifiuids and thus cause precipitation and digestive nate which comprises the steps of reacting equiupsets. molecular proportions of an acid salt of choline products and recovering theophyllin cholinate in which it is soluble, with an alkali metal salt from the filtrate. of the xanthine, also in methanol. The alkali 2. The method of preparing theophyllin cholication of the xanthine salt and the acid anion nate which comprises the steps of reacting equiof the choline salt combine to form the salt molecular proportions of choline chloride and potassium theophyllinate, each dissolved in cholinate thus produced remains in solution. methanol, removing the precipitate of potassium The precipitate is removed, as by filtration, and chloride from the theophyllin cholinate in sothe solvent is evaporated from the filtrate to lution and evaporating the solution to dryness. yield the xanthine cholinate in dry powder form. PETER CLAUDE HERELD.

As a specific example for producing theophyllin cholinate (theophylline hydroxyethyltrimethylamine), equimolecular proportions of No references cited. 

1. THE METHOD OF PREPARING THEOPHYLLIN CHOLI NATE WHICH COMPRISES THE STEPS OF REACTING EQUIMOLECULAR PROPORTIONS OF AN ACID SALT OF CHOLINE AND AN ALKALI METAL SALT OF THEOPHYLLINE, EACH DISSOLVED IN METHANOL, FILTERING THE REACTION PRODUCTS AND RECOVERING THEOPHYLLIN CHOLIATE FROM THE FILTRATE. 